Resveratrol reversed ambient particulate matter exposure-perturbed oscillations of hepatic glucose metabolism by regulating SIRT1 in mice.

Abstract

Much evidence has shown that ambient particulate matter (PM) exposure is associated with abnormal glucose metabolism, but the underlying mechanism has not yet been fully characterized. Circadian disruption has adverse effects on glucose metabolism. In this study, we investigated the effects of long-term ambient PM exposure on the hepatic circadian clock and the expression rhythm of genes associated with hepatic glucose metabolism in mice. C57BL/6 mice were exposed to filtered air (FA), ambient PM, or ambient PM plus resveratrol (RES). After 15weeks (12h per day, 7days per week) of exposure, glucose homeostasis, the rhythmic expression of clock genes, and genes associated with hepatic glucose metabolism were determined. Our results found that PM exposure induced glucose metabolism disorder and perturbed the rhythmic mRNA expression of core clock genes and their target genes involved in hepatic glucose metabolism. Mechanistic investigations demonstrated that ambient PM exposure markedly altered the expression patterns of BMAL1, clock, and SIRT1 in vivo. Simultaneously, we demonstrated that RES (an activator of SIRT1) changed the expression pattern of SIRT1, thereby reversing the rhythm misalignment of BMAL1 and clock and hepatic glucose metabolism disorder induced by ambient PM exposure. In addition, PM2.5 exposure perturbed the rhythmic protein expression of BMAL1, clock, and SIRT1 in L-02 cells. Simultaneously, we demonstrated that RES restored the SIRT1 circadian rhythm, which reversed the rhythm misalignment of BMAL1 and clock in L-02 cells induced by PM2.5 exposure. Taken together, our results suggested that long-term ambient PM exposure perturbed the hepatic core circadian clock rhythm and caused glucose metabolism disorder, which could be reversed by RES supplementation. Our study offers a potential application of RES for combating circadian misalignment-related metabolic diseases.